title: Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.
abstract: Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways.
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia. maqusood@gmail.com
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Javed
authors.initials: J
authors.lastname: Ahmad
authors.forename: Javed
authors.initials: J
authors.lastname: Musarrat
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Khedhairy
authors.forename: Mohamad S
authors.initials: MS
authors.lastname: AlSalhi
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents; D005290:Ferric Compounds / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053758:Nanoparticles; D009499:Neutral Red; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D013778:Tetrazolium Salts; D013844:Thiazoles; D014961:X-Ray Diffraction
chemical_list: D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D004396:Coloring Agents; D005290:Ferric Compounds; D007202:Indicators and Reagents; D051034:Inhibitor of Apoptosis Proteins; D017382:Reactive Oxygen Species; D000077022:Survivin; D013778:Tetrazolium Salts; D013844:Thiazoles; C550717:nickel ferrite; D009499:Neutral Red; D012313:RNA; D009532:Nickel; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053453:Caspase 9; C022616:thiazolyl blue; D005978:Glutathione